The purpose of this application is to establish at the University of Iowa Cardiovascular Center a Specialized Center of Research (SCOR) in Hypertension under the co-direction of Drs. Michael J. Brody and Allyn L. Mark. The goals of this SCOR are to provide a coordinated interdisciplinary approach to studies on pathogenesis and consequence of hypertension by more than 20 investigators from 11 departments. The major theme is on factors underlying abnormal neural control of the circulation in hypertension. The approaches are broad, ranging from studies on cellular and molecular mechanisms to control of arterial pressure in hypertensive and prehypertensive humans. Projects IA, B, C, and D involve the neurobiology od CNS mechanisms of arterial pressure and fluid volume regulation and include studies on central neurotransmitter systems, central actions of aldosterone and centers for vasomotor control and fluid regulation. Projects IIA, B and C concern control of renal function and sodium transport and involve studies on actions of endogenous opioids on the kidney, abnormal reno-renal reflexes in hypertension and the new-found role of the papillary collecting duct cells in steroid-mediated sodium transport. Projects IIIA, B, and C emphasize cellular and molecular biological approaches to the development and consequences of hypertension and include evaluation of cellular mechanisms responsible for the neurally- mediated contribution to cardiac hypertrophy, second messengers responsible for growth factor induced responses of vascular smooth muscle cells and the evaluation of humoral control systems whose abnormalities may be present in newborn genetically hypertensive rats. Projects IVA and B concern studies in man and include evaluation of the neurogenic contribution to altered pressure regulation associated with abnormal insulin sensitivity and obesity. Longitudinal studies on adolescents will examine the pre- hypertensive marker of adult hypertension. The research projects are supported intracellular measurements of calcium and pH. The close thematic relation of the research projects and the history of productive collaboration between investigators should lead to significant new information about the causes of hypertensive disease and to the development of effective interventions for prevention and treatment.